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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by davpet on December 30, 2005, at 6:36:11
I am an anti-depressant non-responder . The consensus amongst the medical community is that depression is caused by a lack of the monamines (serotonin;dopamine;norepinephrine) and thus nearly all anti-depressants work in one way or another by increasing the amount of neurtransmitters circulating in your brain . But has anyone considered that depression may be caused by high levels of neutransmitters not low . Let me explain as i'm sure some of you know neurotransmitter receptors work on a system of down-regulation and up-regulation . The more you expose a receptor to its respective neurotransmitter the more it desensitises (down-regulates) thus more neutransmitter is required to get the same amount of activation out the receptor . For example drugs and and binge eating flood your brain with neutransmitters - you feel good for awhile and then crash . Over time this constant flooding desensitises your receptors and now your normal neutransmitters levels are not enough to activate their receptors . It is this deficit that equals depression . So what do you do , you go to a P/doc and what do they say - you don't have enough serotonin etc. and they give you an SSRI. Which floods your brain once again with serotonin which causes further down-regulation worsening the problem.
Posted by jamestheyonger on December 30, 2005, at 14:35:11
In reply to Revolutionary approach to depression, posted by davpet on December 30, 2005, at 6:36:11
"The consensus amongst the medical community is that depression is caused by a lack of the monamines (serotonin;dopamine;norepinephrine) and thus nearly all anti-depressants work in one way or another by increasing the amount of neurtransmitters circulating in your brain"
It is a decades old theory that is not very valid.
Depression is not caused by a defiency of NT's.
AD's have many actions, one is to delay the NT's from being dactivated at the neuron clef or gap.
This should not be over generalized to "increasing the amount of neurotransmitters circulating in your brain". In any case we really know very little about NT's so we are far away from being able to measure them, therefor we don't know what is normal.If slowing reuptake of NT's at the clef where the cause of depression than AD's would be very effective and work quickly. They don't.
Posted by linkadge on December 30, 2005, at 16:45:18
In reply to Re: Revolutionary approach to depression, posted by jamestheyonger on December 30, 2005, at 14:35:11
Your thinking may not be that abnormal. Tianeptine is an antidepressant used in europe with marked anti-anxiety effect.
The paradox with tianaptine is that it acts as a serotonin reuptake accelerator. Ie it works opposite to SSRI's.
Just type tianeptine + paradox into any search engine to read about some of the really interesting ways that doctors have tried to explain this one.
Anyhow, neurotransmitter abnormalities have not been consistantly shown in depression and some of these new findings are demonstrating our lack of knowledge.
I think the argument for neurotransmitter abnormalities was mainly to make the concept of mental illness more acceptable.
Do the mice have abnormal serotonin?
Linkadge
Posted by Phillipa on December 30, 2005, at 20:32:54
In reply to Re: Revolutionary approach to depression, posted by linkadge on December 30, 2005, at 16:45:18
Interesting theory but there may be truth in it. Fondly, Phillipa
Posted by davpet on December 31, 2005, at 10:25:05
In reply to Revolutionary approach to depression, posted by davpet on December 30, 2005, at 6:36:11
The atkins/low carb diet is proven to lower serotonin levels (low insulin levels = low serotonin) . When you first go on this type of type your depression unbelievable worsens, but after 7-10 days your mood starts to improve slowly . Why is this , you haven't increased your carbs ? Simple your brain adjusts to the lower level of serotonin and up-regulates your receptors.
Same thing with benzos the more you take the more you need to get the same effect (due to GABA down-regulation). Stop taking them and you go through hell but evenually your receptors up-regulate and you feel calmer.
Posted by Pfinstegg on December 31, 2005, at 10:42:33
In reply to Re: Revolutionary approach to depression, posted by linkadge on December 30, 2005, at 16:45:18
I've taken tianeptine for a year, after many years of taking SSRI's and antipsychotics. I also use ongoing rTMS treatment, although not as much as I would like, because I live far away from Dr. Hutto in Atlanta. None of this is perfect, but I am a lot less depressed, and also am completely side-effect free. So I think there is something important in what you say- that flooding the intercellular spaces with serotonin may cause a cascade of abnormalities to both transmitters and receptors which, over time, may make our brains less normal than they were before the onset of HPA axis dysregulation and the brain abnormalities associated with that.
Although I began being treated for severe depression 12 years ago, I had never had a suicidal thought until nine years ago- after I had been on SSRI's for three years. Those thoughts persisted endlessly until six months after I stopped the SSRI's one year ago. And I am far from being a child!
The things I'm doing now- tianeptine and TMS- plus psychotherapy, of course, were things I first read about right here on Babble, and then researched as extensively as I could. I was looking for the most neuroprotective things, rather than the latest drug whose long-term efects were unknown. I know my choices wouldn't be the right ones for everyone else, but I am very grateful for learning about them. Luckily, I have a doctor who supports me on all these choices.
Posted by linkadge on December 31, 2005, at 11:38:33
In reply to Re: Revolutionary approach to depression, posted by davpet on December 31, 2005, at 10:25:05
Its so true. The worst times of my life are either going on a drug or coming off a drug, but eventually I feel the same either way.
The brain is extremely sensitive to change.
Thats why I was a member of the drug of the month club, changing the drug was the only thing that improved the mood.
(Perhaps a new haircut would have done the same :) (I know I'm overgeneralizing a tad)
Linkadge
Posted by linkadge on December 31, 2005, at 12:03:57
In reply to Re: Revolutionary approach to depression » linkadge, posted by Pfinstegg on December 31, 2005, at 10:42:33
Hey, I would love to take the path you have taken with regards to Tianeptine.
Anyhow my story is similar. No suicidality untill SSRI's. Suicidiality emerged during treatement and slowly deminished after discontinuing.
There was an arugment about this sort of thing before, but there is acually evidence that a large portion of depressives already have a *less* active serotonin reuptake transporter to begin with. People with one or two short varients of the serotonin transporter seem dominate the depressive population.
People with the long varients have been shown to respond better to SSRI's which makes some sence,
since they have a higher reuptake of serotonin, but these individuals seem to be scarce in the depressed population.http://psychiatry.jwatch.org/cgi/content/full/2003/1008/1
This is a bit long but it tries to explain how people with short serotonin allels may have problems with amygdala circutry due to elevated serotonin, and thus explain their high occurance of depression responces to stressfull life events. (It was funny cause a year back there was a little blib about how it seemed counterintuitive to be prescribing SSRI's to this group of people, they got rid of that blib for some reason)
http://www.psycheducation.org/mechanism/4WhyShortsLongs.htm
Another angle is that there have been many false claims about the neuroprotective properties of antdiepressants. The fact is that this line of thinking was spurred by studies with Tianeptine. A lot of doctors just assumed it carried over to other drugs as well. But SSRI's do NOT confer the same neuroprotective properties as tianeptine, and that is an important distinction to make.
p.s. I hope to one day be able to try tianeptine.
Linkadge
Posted by flmm on December 31, 2005, at 13:11:05
In reply to Re: Revolutionary approach to depression, posted by linkadge on December 31, 2005, at 12:03:57
I think proper balance is the key to all these chemical interactions. Getting too technical probably leads to nowhere!
Posted by Jakeman on December 31, 2005, at 16:19:31
In reply to Re: Revolutionary approach to depression, posted by linkadge on December 31, 2005, at 12:03:57
>A lot of doctors just assumed it carried over to other drugs as well. But SSRI's do NOT confer the same neuroprotective properties as tianeptine, and that is an important distinction to make.
>I've only read the press release, but it is my understanding that a recent John Hopkin's study showed that SSRI's (fluoxetine) do in fact confer the similar neuroprotective properties as tianeptine.
http://www.dr-bob.org/babble/20051221/msgs/591763.htmlwarm regards ~Jake
Posted by linkadge on December 31, 2005, at 16:56:39
In reply to Re: Revolutionary approach to depression » linkadge, posted by Jakeman on December 31, 2005, at 16:19:31
I am not saying that fluoxetine is not neurotrophic, (ie. I agree it can grow new neurons).
The SSRI's however, don't seem to share Tianeptine's neuroprotective ability, ie the ability to prevent stress induced hippocampal atrohpy.
See:
http://www.biopsychiatry.com/tianep.htm
http://www.jneurosci.org/cgi/content/full/22/9/3638
Also, some discussion at:http://ajp.psychiatryonline.org/cgi/content/full/161/7/1309-a
Linkadge
Posted by Pfinstegg on December 31, 2005, at 17:50:59
In reply to Re: Revolutionary approach to depression, posted by linkadge on December 31, 2005, at 16:56:39
Thanks, Link! Your posts have been some of the most informative and helpful. You really do a lot of reading! I guess we all have to come up against the painful fact that we have had brain changes because of HPA axis dysregulation, and that there really isn't the kind of treatment for us that we would like, yet. But a lot of good, smart people are working on it. The medical reprints from Rockefeller University and the German Primate Center were the principle ones in helping me make treatment choices. I hope that in a few years we will have more choices- I think we will.
I was startled to read a study about rats, bred for either low or high anxiety at the German Primate Center, and treated with Prozac from birth. The low-anxiety rats were unaffected, but the high anxiety rats treated with Prozac showed all the signs of depression at one year (giving up quickly on the forced-swim test, and other tests). The untreated high-anxiety rats, raised naturally with their mothers, did not show any impairments when tested at a year; they did as well as the animals bred for low anxiety. It raised a huge question in my mind: are the SSRI's actually worsening the situation in people already stressed enough to have developed unfavorable brain changes, such as
an underactive left frontal lobe, a smaller left hippocampus, and sparser or damaged- appearing CA3 neurons. And other things involving glutamate, and probably numerous other things which i don't know enough about to talk about.I hope you will give tianeptine a try. It's not a powerful AD, in the sense of making you feel great, but i do feel much more like the old pre-depression me- and that means so much. I could certainly be wrong, but I feel that it is helping my hippocampus be at least a bit more like it used to be. Several years ago, the left side was about 20% smaller than normal by MRI. I'm not expecting that it will grow back to a normal size, but I do think it's helping the neurons that I do have be healthier- and perhaps I am growing a few! TMS has very similiar actions- the hippocampal neurons look healthier. It also down-regulates the HPA axis, whereas the tianeptine acts more to protect excessive cortisol from damaging the neurons. At least, I think that's what I learned!
Posted by Phillipa on December 31, 2005, at 18:34:11
In reply to Re: Revolutionary approach to depression, posted by linkadge on December 31, 2005, at 16:56:39
Okay so does this mean that SSNRI's are the same and cause depression to worsen ? Fondly,Phillipa
Posted by linkadge on December 31, 2005, at 19:14:39
In reply to Re: Revolutionary approach to depression » linkadge, posted by Pfinstegg on December 31, 2005, at 17:50:59
I remember that study, it was entitled something like "mice raised on prozac grow up depressed" or something.
It is my understanding that serotonin can be both anxiolytic and anxiogenic. The amygdala is loaded with 5-ht2a receptors, for instance.Medicinal herbs usually have all sorts of interesting receptor binding. For instance marajuanna, acts to agonize 5-ht1a, but antagonize 5-ht2a, and 5-ht3.
I have a feeling that SSRI's can make things worse for some people due to the fact that the drugs increase serotonin in the amygdala.
Certain other antidepressant compound show more selectivity. For instance rTMS and ECT increase hippocampal serotonin, but don't really affect serotonin in too many other regions.
This following study was interesting, it demonstrated rTMS induced changes in high anxiety mice only.
http://www.wireheading.com/rtms/rats.html
I wonder how my doctor would react to a Tianeptine request?
Linkadge
Posted by Pfinstegg on January 1, 2006, at 9:49:22
In reply to Re: Revolutionary approach to depression, posted by linkadge on December 31, 2005, at 19:14:39
Well, it's hard to say! Mine was completely blank when I first suggested it, but became very supportive after he read the reprints I gave him. I'm sure things wouldn't have happened this way if I had not had a miserable time with him over many years of SSRI's and APs. He is just as happy as I am that I'm no longer suicidal, and have mild to moderate depression- and sometmes even none- rather than a relentlessly severe one. But, of course, he can't prescribe it- you have to find it.
Posted by Pfinstegg on January 1, 2006, at 9:58:54
In reply to Re: Revolutionary approach to depression, posted by Phillipa on December 31, 2005, at 18:34:11
Not necessarily at all. The down-side of SSRI's -for some people, only, has only become apparent after many years of use. The SNRI's are pretty new, and, if there are any similiar effects with their use, it would be hard to know it so soon. If they are helping, That is wonderful. I wouldn't worry, but would just try to be aware of the remote possibility.
Posted by linkadge on January 1, 2006, at 12:20:33
In reply to Re: Revolutionary approach to depression » linkadge, posted by Pfinstegg on January 1, 2006, at 9:49:22
I don't know how these things work. Is is legal to import Tianeptine into Canada/U.S.?
Linkadge
Posted by Pfinstegg on January 1, 2006, at 12:31:33
In reply to Re: Revolutionary approach to depression » linkadge, posted by Pfinstegg on January 1, 2006, at 9:49:22
Yes. Just not to the UK.
Posted by JahL on January 2, 2006, at 0:28:17
In reply to Re: Revolutionary approach to depression, posted by Pfinstegg on January 1, 2006, at 12:31:33
> Yes. Just not to the UK.
I suppose it's class C, but in reality you're very unlikely to encounter any problems. Confiscation is the worst that can happen. I imported Tianeptine (along with numerous other meds) into the UK - and with the blessing of my pdoc.
FTR, it didn't help, but was noticeably side-effect free, in stark contrast to the other 20 or so ADs I've tried.
J.
Posted by ed_uk on January 2, 2006, at 5:12:44
In reply to Re: Revolutionary approach to depression, posted by JahL on January 2, 2006, at 0:28:17
Hi J
Class C? I didn't think tianeptine was controlled in the UK.
Regards
Ed
Posted by RedSoxFan79 on January 3, 2006, at 0:07:28
In reply to Re: Revolutionary approach to depression » JahL, posted by ed_uk on January 2, 2006, at 5:12:44
Lamictal is effective for me against depression, much more than SSRIS and supposedly one of its actions besides inhibiting glutamate release is inhibiting monoamine release....
This is the end of the thread.
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